Fetal tissue sampling--indications,techniques, complications,and experience with sampling of fetal skin,liver, and muscle.

Invasive prenatal testing has become an important way to evaluate fetuses at increased risk for hereditary disorders. In utero sampling of fetal skin, liver, and muscle may be required to diagnose before-birth disorders that cannot be diagnosed by analysis using chorionic villi or amniotic fluid. In the next few years, many of these conditions will be detected by DNA analysis, and the need for these procedures may decrease dramatically. First performed by fetoscopy, fetal tissue sampling is now most frequently done by inserting a biopsy needle under continuous ultrasonographic guidance. We describe the indications, techniques, complications, and experience with obtaining fetal skin, liver, and muscle biopsy specimens.     

Earth, sky, wind, and weather

This paper seeks to understand what it means to live 'in the open'. It begins with an account of experiments that test whether children have acquired a scientifically correct understanding of the shape of the earth, according to which people live all around on the outside of a solid sphere. This understanding cannot accommodate the phenomenon of the sky, in relation to which the earth can appear only as the ground of human habitation. James Gibson's ecological approach to perception offers a possible alternative, depicting earth and sky as complementary hemispheres. Yet for Gibson, this earth-sky can be inhabited only insofar as it is furnished with objects. To that extent, it ceases to be open. Drawing on elements of Merleau-Ponty's phenomenology, it is argued that in the open world persons and things relate not as closed forms but by virtue of their common immersion in the generative fluxes of the medium – in wind and weather. Fundamental to life is the process of respiration, by which organisms continually disrupt any boundary between earth and sky, binding substance and medium together in forging their own growth and movement. Thus to inhabit the open is not to be stranded on the outer surface of the earth but to be caught up in the transformations of the weather-world.     

Magnesium,calcium, copper,and zinc in meals

Meals of 12 diets were prepared from conventional foods with precautions against contamination by metallic elements because of epidemiologic associations between ischemic heart disease and the metabolism of magnesium, calcium, copper, and zinc. Magnesium, calcium, copper, and zinc were measured by atomic absorption spectrometry with satisfactory accuracy and precision. The mean daily amount of copper in the diets was less than the apparent adult requirement. Mean amounts of magnesium and zinc were close to apparent requirements; however, adults consuming amounts less than one standard deviation below these means may be depleting body stores and be at risk of pathology. Magnesium and copper were highly correlated (r=0.849,P=0.0001) in meals. This and other significant correlations probably will prevent the relationships of these elements to ischemic heart disease from being elucidated by epidemiology. Metabolic experiments will be necessary to differentiate among several hypotheses.     

Genome analysis,phylogeny, and classification

The implications of genome analysis for evolutionary theory and systematics are treated. The precise relationship between the theoretical and operational definitions of chromosome homology is shown to be uncertain. It is pointed out that genera defined by genome analysis may be either monophyletic or non-monophyletic, and that the genus is not a basic unit of evolution. Characters obtained by genome analysis may be useful in a phylogenetic context, provided they are treated as all other characters.     

Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and jasmonates

Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins, ethylene, gibberellins, and jasmonates, are involved in all aspects of plant growth, and developmental processes as well as environmental responses. However, our understanding of hormonal homeostasis is far from complete. Phytohormone conjugation is considered as a part of the mechanism to control cellular levels of these compounds. Active phytohormones are changed into multiple forms by acylation, esterification or glycosylation, for example. It seems that conjugated compounds could serve as pool of inactive phytohormones that can be converted to active forms by de-conjugation reactions. Some conjugates are thought to be temporary storage forms, from which free active hormones can be released after hydrolysis. It is also believed that conjugation serves functions, such as irreversible inactivation, transport, compartmentalization, and protection against degradation. The nature of abscisic acid, brassinosteroid, ethylene, gibberellin, and jasmonate conjugates is discussed.     

Effects of GTP,forskolin, sodium fluoride,serotonin, dopamine,and carbachol on adenylate cyclase inTeleost retina

Adenylate cyclase activity can be stimulated in goldfish retina by forskolin, GTP, NaF, dopamine and serotonin. Pharmacological characterisation of the dopamine and serotonin responses shows them to be mediated through specific receptors. A synergistic increase in the level of C-AMP is observed following application of forskolin together with NaF, GTP, dopamine, or serotonin. Dopamine and serotonin with or without GTP produced an additive response. When NaF and GTP are both together their combined effect in elevating C-AMP levels in the presence or absence of forskolin is less than additive. These results suggest that forskolin may be interacting with a G_s protein as well as directly stimulating adenylate cyclase. Increases in the level of C-AMP observed following application of forskolin or dopamine are decreased by carbachol in a dose-dependent manner. The carbachol response is blocked by pertussis toxin and is insensitive to the phosphodiesterase inhibitor, IBMX, suggesting an involvement of a G_i protein. Carbachol attenuation of elevated C-AMP levels is inhibited by atropine while pirenzapine has little effect suggesting the presence of a M2-type receptor.     

COMPOSITE TRAITS,SELECTION RESPONSE,AND EVOLUTION

It is very difficult to relate macroevolutionary patterns to the microevolutionary processes described by quantitative-genetic models. Quantitative-genetic parameters are statistical abstractions. Their long-term significance and evolution might be understood if they can be related to development, physiology, and other biological properties. Most continuous traits are composites of other traits that may contribute differentially to selection response and long-term divergence. The operation of selection on continuous traits can be indirect, with intermediate optima caused by correlated fitness components. Few realistic models are available, and heritable maternal effects can further complicate selection response. Examples involving allometry of brain and body size in mammals suggest that prenatal and postnatal growth have contributed differently to body-size evolution, with different correlated changes in brain size. Several different models could explain these patterns, and interpretation is further complicated by statistical difficulties in comparative biology. Quantitative-genetic models may become more informative and predictive if variation in their parameters can be explained by developmental and other biological processes that have been shaped by the previous history of the population.     

Structure of Sydowinin A,Sydowinin B,and Sydowinol,Metabolites from Aspergillus sydowi

The structures of sydowinin A, sydowinin B, and sydowinol were established by chemical and spectroscopic data. Sydowinin A was shown to be methyl-1-hydroxy-3-hydroxymethyl-xanthone-8-carboxylate (I) and sydowinin B to be methyl-1,7-dihydroxy-3-hydroxymethyl-xanthone-8-carboxylate (VIII). Sydowinol was shown to be represented by formula XIII.     

AIDS, gays, and state coercion

Mohr argues that coercive government policies in response to the AIDS crisis are unjustified and pose a serious threat to the rights of homosexuals. AIDS presently can be transmitted only to those whose actions place them at risk. Paternalistic state coercion is warranted only when a person has diminished capacity or when necessary to prevent someone from ceasing to be an independent agent. Furthermore, an individual may regard sex as a central value. Finally, using public health as a rationale for closing bathhouses or otherwise regulating sexual behavior is a step toward totalitarianism, because coercion is unwarranted when protection from a disease can be achieved by individual action and because the public good served by reducing the size of the pool of AIDS-exposed people is outweighed by the unjust discrimination involved in using coercive measures that affect only certain individuals.     

Reaction of peroxyacetyl nitrate with cysteine,cystine, methionine,lipoic acid,papain, and lysozyme

Peroxyacetyl nitrate was reactive with small molecular-weight sulfur-containing compounds The order of susceptibility was cysteine > reduced lipoic acid = reduced lipoamide > oxidized lipoic acid > oxidized lipoamide > methionine ? cystine. From thiols the predominant product was disulfide. In the early stages of oxidation methionine yielded methionine sulfoxide. Products of oxidation of oxidized lipoic acid and lipoamide were the respective sulfoxides. Cystine was resistant to oxidation, yielding cysteic acid when oxidation took place.Papain was readily inactivated by peroxyacetyl nitrate while lysozyme was resistant. The small amount of inactivation of lysozyme was correlated with methionine oxidation. Papain inactivation was correlated with thiol oxidation and could be reversed by thiol compounds. The oxidation product was judged to be a dimer by methods for determining molecular weight.     

Nitrite, nitrosamines, and cancer.

Carcinogenic N-nitroso compounds are formed from the reaction of naturally-occurring amines and nitrites that may be added to foods or produced by bacterial reduction of nitrate. N-Nitroso compounds can be produced during processing, storage and preparation of foods and in the mammalian stomach. Factors that influence the rates of nitrosation reactions include pH, temperature, catalysts, and inhibitors. Predictions of the extent of nitrosation are complicated by these factors and ultimately the amounts and types of N-nitroso compounds present must be determined by direct analysis. Methods for detection and estimation of volatile nitrosamines are available and low levels (parts per billion) have been found in some cured meat and fish products. General methods for detection of all N-nitroso compounds are not available yet, but are under development. Evaluation of the risk to human populations from these compounds is difficult in the absence of more comprehensive data on their environmental distribution.     

BAG1 modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution

Bcl-2-associated athanogene-1 (BAG1) is a multifunctional protein delivering chaperone-recognized unfolded substrates to the proteasome for degradation. It has been shown to be essential for proper CNS development in vivo, playing a crucial role in neuronal survival and differentiation. With regard to Huntington's disease, a sequestration of BAG1 into inclusion bodies and a neuroprotective effect in double transgenic mice have been reported. Here, we show that BAG1 reduces aggregation and accelerates degradation of mutant huntingtin (htt-mut). Moreover, it reduces nuclear levels of htt-mut. This effect can be overcome by over-expression of seven in absentia homolog 1, an E3 ligase negatively regulated by BAG1 and known to be involved in nuclear import of htt-mut. In vivo , BAG1 proved to be protective in a Drosophila melanogaster Huntington's disease model, preventing photoreceptor cell loss induced by htt-mut. In summary, we present BAG1 as a therapeutic tool modulating key steps in htt toxicity in vitro and ameliorating htt toxicity in vivo .     

Caveolae: Formation,dynamics, and function

Caveolae are abundant surface pits formed by the assembly of cytoplasmic proteins on a platform generated by caveolin integral membrane proteins and membrane lipids. This membranous assembly can bud off into the cell or can be disassembled releasing the cavin proteins into the cytosol. Disassembly can be triggered by increased membrane tension, or by stress stimuli, such as UV. Here, we discuss recent mechanistic studies showing how caveolae are formed and how their unique properties allow them to function as multifunctional protective and signaling structures.     

Extrapolation, uncertainty factors, and the precautionary principle

This essay examines the relationship between the precautionary principle and uncertainty factors used by toxicologists to estimate acceptable exposure levels for toxic chemicals from animal experiments. It shows that the adoption of uncertainty factors in the United States in the 1950s can be understood by reference to the precautionary principle, but not by cost-benefit analysis because of a lack of relevant quantitative data at that time. In addition, it argues that uncertainty factors continue to be relevant to efforts to implement the precautionary principle and that the precautionary principle should not be restricted to cases involving unquantifiable hazards.     

Defining specificities,genes, antigens,and antibodies- A matrix approach

We study the consequences of assigning single letter symbols to operationally defined entities such as genes, antigens, specificities, and antibodies. If this is to be done and if reagents are not specific in recognizing the products of single genes or single antigens, then these entities must be defined by a definition matrix to avoid mislabeling a matrix of data. A method is given whereby for a given matrix of data all possible definition matrices consistent with this data can be obtained. In particular, all the ways of labeling by the complex-complex code of Hirschfeld can be so obtained.     

Partition structures, Polya urns, the Ewens sampling formula, and the ages of alleles

It has recently been shown that the Ewens sampling formula may be generated by a Polya-like urn model. A genealogical proof of this result equates the labelling of balls in the urn to the partition by age of alleles in the sample. This urn construction is shown to be equivalent to the construction of Kingman (Proc. Roy. Soc. London Ser. A 361 (1978), 1-20) using a Poisson-Dirichlet "paintbox" and as a consequence, the partition by ages is seen to be equivalent to the size biased permutation of the Poisson-Dirichlet distribution. This approach unifies and extends many results on ages of alleles, the Polya urn, and the Poisson-Dirichlet distribution. Furthermore the Ewens sampling formula is characterized as being the only partition structure which may be generated by an urn-like mechanism.     

Life,information theory,probability, and physics

A purely information-theoretical approach to the problem of self-replication of elementary living units implies that pure chance is the determining factor in the formation of the first living unit. The probability of such a spontaneous formation can be calculated from the minimum amount of information which an organism must possess in order to replicate itself. An estimation of this amount of information is made here by two different methods. First by a “paper and pencil experiment” which indicates the minimum amount of information needed on a printed page in order that with given tools the page could be reproduced. Second—by an analytical consideration of some hypothetical molecular mechanisms. A general method for handling such problems is suggested. On the basis of estimated information contents it is shown that under most favorable conditions the probability of a spontaneous generation by pure chance during the lifetime of the earth is vanishingly small. It is concluded that dynamic factors, which may reduce tremendously the information content, must play a role in the genesis of life on earth.     

Mechanism of D-cycloserine action: transport systems for D-alanine, D-cycloserine, L-alanine, and glycine

The accumulation of d-alanine, l-alanine, glycine, and d-cycloserine in Escherichia coli was found to be mediated by at least two transport systems. The systems for d-alanine and glycine are related, and are separate from that involved in the accumulation of l-alanine. d-Cycloserine appears to be primarily transported by the d-alanine-glycine system. The accumulation of d-alanine, glycine, and d-cycloserine was characterized by two line segments in the Lineweaver-Burk analysis, whereas the accumulation of l-alanine was characterized by a single line segment. d-Cycloserine was an effective inhibitor of glycine and d-alanine accumulation, and l-cycloserine was an effective inhibitor of l-alanine transport. The systems were further differentiated by effects of azide, enhancement under various growth conditions, and additional inhibitor studies. Since the primary access of d-cycloserine in E. coli is via the d-alanine-glycine system, glycine might be expected to be a better antagonist of d-cycloserine inhibition than l-alanine. Glycine and d-alanine at 10(-5)m antagonized the effect of d-cycloserine in E. coli, whereas this concentration of l-alanine had no effect.     

Caprine blood groups. 2. The C,G, H,I, J,K, L,N, and Q systems

Nine blood group systems of goats were identified using 12 caprine reagents produced by absorption of alloimmune antisera. The caprine C blood group system, possibly homologous to the ovine C blood group system, was characterized by two reagents and shown to be controlled by three alleles,C ¹²,C ²⁵, andC ⁻. A more complex blood group system of goats, designated G, was identified using three reagents and shown to be controlled by six codominant alleles (G ^10.19.20,G ^10.19,G ^10.20,G ¹⁰,G ¹⁹,G ²⁰) and a recessive allele (G ⁻). A further seven one-factor two-allelic systems were identified by seven reagents. The nine genetic systems provided exclusion probabilities of 0.479, 0.492, 0.548, and 0.572 in Australian Angora, Dairy, Cashmere, and Texan Angora goat breeds, respectively. This work was supported by a grant from the Australian Stud Book, Alison Road, Randwick, New South Wales 2031, Australia.